title: Intensive short-term treatment with rituximab, cyclophosphamide and methylprednisolone pulses induces remission in severe cases of SLE with nephritis and avoids further immunosuppressive maintenance therapy.
abstract: BACKGROUND
  B cells play a central role in systemic lupus erythematosus (SLE). Rituximab is expected to induce apoptosis of all the CD20-positive B cells. A proportion of patients are refractory or intolerant to standard immunosuppression. These are candidate to new therapeutic options.
  
  
  METHODS
  Eight patients [six women, two men, mean age 41-year-old (27-51), with severe multiorgan involvement (kidney, skin, nervous system, polyarthritis, polyserositis, antiphospholipid antibody syndrome)] were considered eligible for an intensive combination therapy including rituximab. Rituximab was administered (dose 375 mg/m(2)) on Days #2, 8, 15 and 22. Two more doses were administered 1 and 2 months following the last weekly infusion. This treatment was combined with two pulses of 750 mg cyclophosphamide (Days #4 and 17) and three pulses of 15 mg/kg (Days #1, 4 and 8) methylprednisolone followed by oral prednisone, 50 mg for 2 weeks rapidly tapered until 5 mg in 2 months. Response was evaluated by assessing the changes in clinical signs and symptoms [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI score)] and laboratory parameters for at least 12 months.
  
  
  RESULTS
  Levels of erythrocyte sedimentation rate and anti-double-strand DNA antibodies significantly decreased (P < 0.01 at 12 months), whereas C3 and mainly C4 values increased at 6 months (P < 0.01 for C4). Proteinuria improved in the cases with renal involvement (P < 0.01 at 3, 6 and 12 months). SLEDAI score improved moving from the mean 17.3 (12-27) before therapy to 3.1 (1-5) after rituximab treatment. Constitutional symptoms including arthralgia, weakness and fever disappeared in all the previously affected patients; paresthesia improved in the four patients with polyneuropathy and skin lesions gradually resolved in the patients with necrotizing skin ulcers at presentation. Drug side effects were negligible.
  
  
  CONCLUSIONS
  Long-lasting remissions were obtained in patients with severe SLE and major organ involvement by this intensive administration of rituximab combined with low doses of intravenous cyclophosphamide and methylprednisolone pulses followed by a rapid tapering of prednisone to 5 mg/day as a sole maintenance therapy.
authors.affiliation: Universita di Torino, Torino, Italy. dario.roccatello@unito.it
authors.forename: Dario
authors.initials: D
authors.lastname: Roccatello
authors.forename: Savino
authors.initials: S
authors.lastname: Sciascia
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossi
authors.forename: Mirella
authors.initials: M
authors.lastname: Alpa
authors.forename: Carla
authors.initials: C
authors.lastname: Naretto
authors.forename: Simone
authors.initials: S
authors.lastname: Baldovino
authors.forename: Elisa
authors.initials: E
authors.lastname: Menegatti
authors.forename: Rita
authors.initials: R
authors.lastname: La Grotta
authors.forename: Vittorio
authors.initials: V
authors.lastname: Modena
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy*; D008181:Lupus Nephritis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D013997:Time Factors
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D005938:Glucocorticoids; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D008775:Methylprednisolone